Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 1,225 records · Page 68Linked to original sources

PubMed1993

Profile of capsaicin-induced mouse ear oedema as neurogenic inflammatory model: comparison with arachidonic acid-induced ear oedema.

1. We have investigated the mechanism of capsaicin-induced mouse ear oedema compared with that of arachidonic acid (AA)-induced ear oedema, and evaluated the possible involvement of neuropeptides in the development of capsaicin-induced oedema. 2. Topical application of capsaicin (0.1-1.0 mg per ear) to the ear of mice produced immediate vasodilatation and erythema followed by the development of oedema which was maximal at 30 min after the treatment. This oedema was of shorter duration with less swelling than AA-induced oedema (2.0 mg per ear). 3. Capsaicin-induced ear oedema was unaffected when inhibitors of arachidonate metabolites including platelet activating factor (PAF) were administered before capsaicin (250 micrograms per ear) application, while these agents significantly prevented AA-induced oedema. Dexamethasone, histamine H1 and/or 5-hydroxytryptamine (5-HT) antagonists, and substance P (SP) antagonists were effective in inhibiting both models. Furthermore, a Ca(2+)-channel blocker and the capsaicin inhibitor, ruthenium red, were effective inhibitors of capsaicin oedema but had no effect on AA-induced oedema. 4. Phosphoramidon (50 micrograms kg-1, i.v.), an endopeptidase inhibitor, markedly (P < 0.001) enhanced only capsaicin-induced ear oedema, but bestatin (0.5 mg kg-1, i.v.), an aminopeptidase, failed to enhance oedema formation. 5. Neuropeptides (1-100 pmol per site) such as rat calcitonin gene-related peptide (CGRP), SP, neurokinin A (NKA), and vasoactive intestinal peptide (VIP), which are released from capsaicin-sensitive neurones, caused ear oedema by intradermal injection. Furthermore, a synergistic effect of CGRP (10 fmol per site) and SP (10 pmol per site) on oedema formation was observed. 6. The oedema induced by neuropeptides was significantly (P<0.05 or P<0.001) inhibited when cyproheptadine (20 mg kg-1, p.o.), a histamine H, and 5-HT antagonist, was administered before injection. In contrast, nifedipine (50 mg kg-1, p.o.), a Ca2+-channel blocker, and indomethacin(10 mg kg-1, p.o., except for NKA), a cyclo-oxygenase inhibitor, had little effect on neuropeptide induced oedema.7. These results suggest that the mechanism of capsaicin-induced ear oedema is different from that of AA-induced oedema and suggest that the development of capsaicin-induced ear oedema is primarily mediated by neuropeptides. The neuropeptides released after activation of sensory nerves cause an increase of vascular permeability by interactions with endothelial cells and by histamine (and 5-HT)release from mast cells.

Administration, Cutaneous↗

PubMed1993

Inhibition of rat acute inflammatory paw oedema by dihemiphthalate of glycyrrhetinic acid derivatives: comparison with glycyrrhetinic acid.

The anti-inflammatory profile of dihemiphthalate compounds of glycyrrhetinic acid derivatives in acute rat paw oedema induced by various vasoactive agents was compared with the parent compound. Three dihemiphthalate compounds (the di-sodium salt of 18 beta-olean-12-ene- 3 beta,30-diol di-O-hemiphthalate, 18 beta-olean-9(11),12-dione-3 beta,30-diol di-O-hemiphthalate and olean-11,13(18)-diene-3 beta,30-diol di-O-hemiphthalate), significantly inhibited development of carrageenan-induced rat paw oedema during the first 3 h (ED50 70, 90, and 108 mg kg-1 respectively, p.o.), while glycyrrhetinic acid (ED50, 200 mg kg-1) showed a significant inhibition of paw oedema 3 h after carrageenan treatment. The dihemiphthalate compounds also suppressed mouse paw oedema induced by histamine, bradykinin, and PAF acether at doses of less than 100 mg kg-1. However, these compounds failed to inhibit 5-HT-induced mouse paw oedema. Glycyrrhetinic acid had little effect on mouse paw inflammation induced by the above irritants. The three compounds at 10(-7)-10(-4) M, inhibited histamine-induced contraction of guinea-pig isolated ileum. However, concentration-response curves to 5-HT and bradykinin were not affected by the same compounds. These results suggest that the dihemiphthalate compounds modulate vascular permeability caused by endogenous vasoactive agents as one of the anti-inflammatory mechanisms. This action is quite different from that of glycyrrhetinic acid.

Animals↗

PubMed1993

NF-IL6 represses early gene expression of human papillomavirus type 16 through binding to the noncoding region.

The expression of human papillomavirus type 16 (HPV16) early genes, including E6 and E7 transforming genes, is regulated by several cellular factors binding to the noncoding region (NCR), such as the glucocorticoid receptor, NF-I, and AP1, all of which are positive regulators. We demonstrated that the nuclear factor for interleukin 6 expression (NF-IL6) specifically binds to the HPV16 NCR ranging from nucleotides 7007 to 7766 and represses the early gene expression of HPV16. The responsive element in HPV16 NCR was determined within the region ranging from nucleotides 7454 to 7766. In this region, many binding sites for other cellular transactivators, such as NF-I and AP1, have been detected. Interestingly, three of seven binding sites for NF-I and two of two binding sites for AP1 in this region overlap with the putative NF-IL6 binding sites identified by computer analysis. Competition experiments with the oligonucleotides containing such NF-I or AP1 sites indicated that NF-IL6 certainly binds to them. Furthermore, in a chloramphenicol acetyltransferase assay using mutant NF-IL6 expression vectors, the DNA binding domain of NF-IL6 was shown to be necessary for repression, whereas the functional domain was not. These findings indicate that repression may be caused by competition with other transcriptional activators, such as NF-I and AP1. Thus, NF-IL6 may play a significant role in the regulation of viral transcription as a part of the host's resistance to viral infection.

Acute-Phase Reaction↗

PubMed1993

Neuropeptide Y inhibits neurogenic inflammation in guinea pig airways.

We examined the effect of neuropeptide Y (NPY) on neurogenic airway microvascular leakage. Male Dunkin-Hartley guinea pigs (250-350 g) were anesthetized with urethan (2 g/kg ip). The cervical artery and vein were cannulated for monitoring blood pressure and injecting drugs, respectively. Atropine and propranolol (each 1 mg/kg i.v.) were administered 30 min before the experiment. After pretreatment with saline (vehicle for NPY) or NPY (1-100 micrograms/kg i.v.), Evans blue dye (30 mg/kg iv) was administered. Then, bilateral vagal nerves were electrically stimulated (5 V, 7 Hz, 5-ms duration for 3 min) to induce airway plasma leakage. Airways were divided into four sections [trachea (Tr), main bronchi, central intrapulmonary airways (IPA), and peripheral IPA] and incubated in formamide (37 degrees C for 16 h). The concentration of Evans blue dye was measured by spectrophotometer. Furthermore, we examined the effect of NPY on exogenous substance P- (0.3 microgram/kg i.v.) induced plasma extravasation. Bilateral vagal stimulation significantly increased leakage of dye in Tr to peripheral IPA. NPY did not affect basal leakage but did significantly inhibit neurogenic plasma extravasation in a dose-dependent manner with maximal inhibitions of 42.3 (Tr), 67.7 (main bronchi), 38.2 (central IPA), and 26.3% (peripheral IPA) at 30 micrograms/kg. Exogenous substance P-induced plasma extravasation was not inhibited by NPY. We conclude that NPY inhibits neurogenic inflammation by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals.

Adrenergic beta-Antagonists↗

PubMed1993

A Ki-1-positive cell line expressing Epstein-Barr virus antigens, established from a child with Ki-1-positive lymphoma.

We report here the establishment of a CD30 (Ki-1) antigen-positive cell line 'Ki-JK' from a child with anaplastic large cell lymphoma. We characterized this cell line and show that: (i) Ki-JK cells do not grow in soft agar but infrequently produce a tumor or suppressed growth when injected into nude mice; (ii) Ki-JK cells expressed Epstein-Barr virus (EBV) antigens, EBV-associated nuclear antigen-2 and latent membrane protein; (iii) Ki-JK cells are labelled by in situ hybridization using an RNA probe derived from the BamHI W fragment of EBV, and (iv) polymerase chain reaction demonstrates the presence of an EBV BamHI W sequence in DNA of lymphoma and Ki-JK cells. These results suggest an etiological role for EBV in the development of some cases of Ki-1-positive lymphomas.

Adolescent↗

PubMed1993

Adjuvant effect of interleukin-1 on the development of late asthmatic response in guinea pigs.

The adjuvant effect of silica and IL-1 in the development of late asthmatic responses (LARs) in guinea pigs was studied. Different doses of silica or recombinant human (rh) IL-1 (1 microgram) with Ascaris suum were used for the immunization. The serum IL-1 concentration was measured after the immunization. One week after the immunization, antigen was challenged and respiratory resistance (Rrs) was measured. Rrs increased silica dose dependently in the late phase, and the increment of Rrs in the late phase was significantly correlated with the serum IL-1 concentration (p < 0.05). In addition, rhIL-1 administration showed an increase in Rrs at the late phase. Antigen-specific IgE and IgG1 were also measured and were increased in guinea pigs immunized both with silica and rhIL-1.

Adjuvants, Immunologic↗

PubMed1993

Mechanisms of bronchoconstriction after allergen ingestion in sensitized guinea pigs.

We examined whether oral administration of allergen induced bronchoconstriction in sensitized guinea pigs and investigated the mechanisms of bronchoconstriction. The animals had been immunized intraperitoneally with a mixture of Ascaris suum extract and silica gel, and exposed to ozone. They were then challenged with an oral dose of A. suum extract (6 mg/kg), and respiratory resistance (Rrs) was measured up to 7 h. After oral administration of the allergen, an increase in Rrs was observed. The mean values at 1, 3, 5 and 7 h after oral allergen challenge were 150 +/- 21, 149 +/- 11, 151 +/- 12 and 134 +/- 10% of the baseline value, respectively. When saline instead of the allergen was orally administered, almost no significant increase in Rrs was observed up to 7 h. Moreover, in nonsensitized guinea pigs, oral administration of allergen produced no significant increase in Rrs for up to 7 h. When atropine was administered as an aerosol, the increase in Rrs induced by an oral allergen challenge was attenuated. Three of the five atropine-treated guinea pigs showed temporary increases in Rrs immediately after the oral allergen challenge. The mean values of Rrs in the atropine-treated animals challenged with oral allergen at 1, 3, 5 and 7 h were 106 +/- 3, 106 +/- 5, 115 +/- 5 and 102 +/- 4% of baseline value, respectively. In the animals which received oral allergen, the number of neutrophils in bronchoalveolar lavage fluid (BALF) significantly increased 2.0-fold (p < 0.05), while no significant increase in the number of eosinophils, macrophages, or lymphocytes in BALF was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

Involvement of superoxide in ozone-induced airway hyperresponsiveness in anesthetized cats.

To determine whether oxygen radical scavengers inhibit ozone-induced airway hyperresponsiveness, we examined the protective effect of polyethylene glycol-superoxide dismutase (PEG-SOD) and PEG-catalase (PEG-CAT) on ozone-induced airway hyperresponsiveness in cat airways. Twenty-five cats divided into five groups were anesthetized and mechanically ventilated. There was no difference between the groups in baseline airway responsiveness to inhaled acetylcholine (ACh). In the control group, AChPC, the concentration required to produce a doubling increase in baseline pulmonary resistance, was significantly reduced by ozone exposure (2.0 ppm for 2 h); the ratios of AChPC before ozone exposure to after ozone exposure (AChPC ratio) were 14.8 +/- 5.7 (p < 0.001) and 4.80 +/- 1.6 (p < 0.01) 30 and 120 min after exposure, respectively. Local administration of PEG-SOD (2,000 U/kg) into airways partially but significantly prevented ozone-induced airway hyperresponsiveness. The AChPC ratios were 6.2 +/- 1.4 and 1.5 +/- 0.2 30 and 120 min after exposure, respectively, which were significantly different from those of the control group (p < 0.05), whereas PEG-CAT pretreatment (6,000 U/kg) was without effect. Combined pretreatment with PEG-SOD and PEG-CAT had no additional protective effect compared with PEG-SOD alone. PEG-SOD had no direct effect on airway responsiveness to ACh. These results suggest that superoxide may be involved in ozone-induced airway hyperresponsiveness.

Acetylcholine↗

PubMed1993

Antiasthma drug, ibudilast, inhibits neurogenic plasma extravasation in guinea-pig airways.

We examined the effect of ibudilast, an antiasthma drug, on neurogenic microvascular leakage in guinea-pig airways by measuring extravasation of Evans blue dye. After intravenous pretreatment with atropine (1 mg/kg) and propranolol (1 mg/kg), bilateral vagal stimulation significantly increased nonadrenergic noncholinergic (NANC)-mediated leakage of dye in the trachea (Tr), the main bronchi (MB), and the central (cIPA) and peripheral (pIPA) intrapulmonary airways. Ibudilast (1.0 to 100 micrograms/kg given intravenously) did not affect basal leakage, but it significantly inhibited NANC-mediated plasma extravasation in a dose-dependent manner, with a maximal inhibition of 74.0% (Tr, p < 0.05), 89.1% (MB, p < 0.05), 91.4% (cIPA, p < 0.01), and 84.3% (pIPA, p < 0.05) at 100 micrograms/kg. Plasma extravasation induced by exogenous substance P (1 microgram/kg given intravenously) was not inhibited by ibudilast. Glibenclamide, an inhibitor of ATP-sensitive potassium channels, blocked the inhibitory effect of ibudilast. We conclude that ibudilast inhibits neurogenic leakage by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals via an ATP-sensitive potassium channel.

Animals↗

PubMed1993

Coronary artery ectasia--a case report and literature review.

A case report of coronary artery ectasia is presented. A middle-aged man was admitted with sudden onset of respiratory arrest which is a rather rare occurrence. Relevant articles are reviewed, and discussion mainly concerns the etiologic and pathophysiologic point of view.

Coronary Artery Disease↗

PubMed1993

Effect of centrifugal force on growth of mouse osteoblastic MC3T3-E1 cells in vitro.

The effect of biomechanical force on growth of skeletal tissue was studied in monolayer cultures of mouse osteoblastic MC3T3-E1 cells which were centrifuged at 320 g for 15 min to 72 h in a CO2 incubator. Centrifugation of the cells for 30 min in low concentrations (0.3 or 1%) of fetal bovine serum (FBS) caused a two-fold increase of [3H]thymidine incorporation at 20 h from the start of centrifugation. However, centrifugation under 10% FBS caused no increase in [3H]thymidine incorporation into DNA. Under 0.3% FBS, [3H]thymidine incorporation increased in a manner dependent on the period of centrifugation and reached a maximum when the cells were centrifuged for 3 h. Stimulation of DNA synthesis by centrifugation was abolished in the presence of H-7, an inhibitor of protein kinase C. Moreover, conditioned medium collected from the centrifuged cultures increased [3H]thymidine incorporation by two-fold over the basal when added to a quiescent culture of MC3T3-E1 cells. These results suggest that centrifugal force stimulates growth of osteoblastic cells through autocrine secretion of some diffusible growth-promoting activity. On the other hand, centrifugation of the cells inhibited induction by FBS of alkaline phosphatase activity and calcium-uptake, two indices of the differentiated phenotype of osteoblasts.

3T3 Cells↗

PubMed1993

[Quenching of ethidium-DNA fluorescence by novel acridines with antitumor activities. II. The structure-activity relationship in acridines with fluorescence quenching of ethidium-DNA].

In order to elucidate the structure-activity relationship between the antitumor activity and the molecular structure of novel DNA-intercalator acridine derivatives (1a-g and 2a-i in Chart 1), DNA-binding properties (intercalation) of these acridines were examined by quenching in the fluorescence of the ethidium-DNA complex. The mechanism of quenching is caused by the displacement of DNA-bound ethidium by a second DNA binding ligand, acridines. The concentration (C50 value) of acridine necessary to reduce the initial fluorescence of DNA-bound ethidium by 50% showed a good correlation with their antitumor activities. The quenching of fluorescence for acridines was examined using amsacrine (AMSA) as a typical standard of the second DNA-bound ligand, and calf thymus DNA with an apparent site size of two base pair. Some of the acridine derivatives showed more potent quenching of fluorescence than amsacrine (AMSA).

Acridines↗

PubMed1993

[Effects of local anesthetics on rat macrophage phagocytosis].

We examined whether phagocytosis by macrophages (M phi s) is affected by local anesthetics (lidocaine HCl, prilocaine HCl, mepivacaine HCl, tetracaine HCl and procaine HCl). Opsonized zymosan, fetal bovine serum and one local anesthetic were added to each M phi sample. After a 30-min incubation, M phi s were washed to make Giemsa stained slides for counting. The phagocytosis rate was calculated by counting the phagocytosizing M phi s per 200 cells with an optical microscope, and rates for the samples containing local anesthetics were compared with those for the non-treated samples. Inhibition of phagocytosis was reversible, dose-dependent and pH dependent for all local anesthetics. Tetracaine HCl inhibited phagocytosis most and procaine HCl, least. These results suggest that local anesthetics at the level of clinical use inhibit leukocyte phagocytosis and therefore may interfere with the normal function of cells fundamental to host defense.

Anesthetics, Local↗

PubMed1993

Decrease in beta-adrenergic receptors of lymphocytes in spontaneously occurring acute asthma.

To clarify changes in beta-adrenergic receptor (BAR) density in spontaneously occurring acute asthma, BAR binding studies were performed on peripheral blood lymphocytes in eight asthmatic and ten normal subjects. Spirometry also was performed. Maximum binding capacity (Bmax) of BAR in acute asthma was significantly lower by 44.2 percent compared with that in stable asthma; FEV1/FVC ratio decreased by 23.9 percent. The Bmax for acute asthma also was significantly lower than that in normal subjects. The Bmax of BAR in all subjects was significantly correlated with FEV1/FVC ratio and percent FEV1. The percentage decrease in the FEV1/FVC ratio and FEV1 from the stable to acute state for each asthmatic subject did not correlate with corresponding percentage decrease in Bmax. These data demonstrate that BAR density of lymphocytes decreases substantially in acute asthma and, simultaneously, suggest that some factors other than the BAR mechanism contribute to the airway obstruction during acute asthma.

Acute Disease↗

PubMed1993

Historical control data of organ weight and gross findings in F344/DuCrj rats and B6C3F1 mice.

Organ weight and gross postmortem findings of control Fischer 344/DuCrj rats and B6C3F1 mice are presented from subchronic, chronic toxicity and carcinogenicity studies that were conducted over a 9 year period at our center (An-Pyo Center). The mean organ weight of the liver, kidney, spleen and the lung were increased associated with age in both species. The most common findings observed at 109 weeks in both species were thymic atrophy, enlargement of the spleen, dilation of the lumen of the uterus and ovarian cysts. Male and female Fischer 344/DuCrj rats commonly exhibited a granular surface of the kidneys, hypertrophy of and/or nodular pituitary glands and subcutaneous tissue masses. Multiple white patches and hypertrophy or atrophy of the testes, atrophy of the seminal vesicles and prostate and nodules in the pancreas were seen frequently in male rats. Malformative nodule in the liver was a common finding in female rats. The most common lesions seen in both male and female B6C3F1 mice were nodules in the liver and lungs and enlargement of the lymph nodes. Nodules on the preputial gland were commonly seen in the males. Sex differences were evident in the incidence of some of the above findings. These historical data will contribute to analyze the organ weight and gross findings at necropsy in long-term toxicity and carcinogenicity studies.

Animals↗

PubMed1993

Mortality, body weight, food and water consumption, and clinical signs in Slc: B6C3F1 (C57BL/6 x C3H) mice utilized in chronic toxicity and carcinogenicity studies.

In vivo historical control data for Slc: B6C3F1 mice, including mortality, body weight, food and water consumption, and clinical signs and which were obtained from long-term toxicity and carcinogenicity studies (11 male and 12 female studies) conducted at the Biosafety Research Center, Foods, Drugs and Pesticides, (An-Pyo Center) during the last five years are presented. Mean survival at 83 and 109 weeks of age was 96.4% (min: 94.0%, max: 100%) and 79.0% (min: 74.0%, max: 86.0%) in males and 98.7% (min: 96.0%, max: 100%) and 81.7% (min: 70.0%, max: 90.0%) in females, respectively. The maximum mean body weight of males and females was 45.1 +/- 3.1 g (mean +/- S.D.) and 39.2 +/- 4.1 g, respectively. Male mice attained their maximum body weight at 72.7 +/- 4.3 weeks of age and females at 76.2 +/- 5.9 weeks of age. Clinical symptoms increased with age, particularly after week 84, and included: wasting, piloerection and palpable abdominal masses. Hypothermia and auricular pallor were common findings in moribund animals from week 79 to 104 of the studies. The use of in-house, historical control data can prove invaluable in the evaluation and interpretation of experimental results, especially in long-term and life-time studies.

Animal Husbandry↗

PubMed1993

Small airway involvement in mixed connective tissue disease.

We studied pulmonary functions in 17 female patients with mixed connective tissue disease (MCTD) to detect early pulmonary involvement in this disease; in 8 of the 17 patients follow-up studies were also performed at 1.2- to 5.9-year intervals. In the first pulmonary function tests, decreases in vital capacity (VC) and diffusing capacity (DLCO) were observed in 6 (35%) and 8 (47%) patients, respectively. The ratio of forced expiratory volume in one second to VC was normal in all the patients, but pulmonary resistance and static compliance were abnormal in 6 (35%) and 10 (59%) patients, respectively. However, frequency dependence of dynamic compliance was found in all 16 patients tested. Moreover, 4 (24%) of the 17 patients had normal DLCO and DLCO-to-alveolar volume ratio (DLCO/VA). Reductions in DLCO and DLCO/VA were significantly correlated with the disease duration. These results suggest that small airway obstruction is an early and frequent indication of functional pulmonary impairment, and that impairment of alveolar gas exchange is progressive in patients with MCTD.

Adolescent↗

PubMed1993

Second malignant neoplasms after treatment for osteosarcoma: a report of three cases.

We report second malignant neoplasms which developed between 7 and 19 years after treatment in 3 pediatric patients with osteosarcoma. Two patients had been treated with only surgery, and another patient had been treated with a combination of surgery with chemotherapy and radiation therapy for primary lesions. Pediatric patients with osteosarcoma, in particular, require careful long-term follow-up to monitor not only metastases but also development of second malignant neoplasms.

Child↗